The aim of this work is to define genetic determinants of the responses to morphine in mice. In addition, we are examining the role of catecholamine metabolism in the sensitization of mice to morphine, cocaine and methylphenidate. Mutant strains have been identified that differ in their analgesic and motor responses to morphine. We will measure narcotic receptors, enkephalins and beta endorphin levels in several brain regions of mice from the mutant and parental strains. We also plan to measure dopamine turnover and the number of dopamine receptors in mice that have been sensitized to morphine, to methylphenidate and to cocaine.